Medication errors have been estimated to account for more than half of all adverse drug events, and antibiotics are one of the most important causes of adverse drug events, with acute renal failure from nephrotoxic agents being particularly prominent. Errors in the hospital setting tend to relate to prescribing, administration, or monitoring. Error-free use of drugs with a low therapeutic ratio is particularly sensitive to the implementation of effective monitoring that can identify patients at high risk for an adverse drug event, detect early signs of an adverse drug event, and tailor dosing to a patient's ability to metabolize and excrete drugs. Aminoglycoside antibiotics are ideal drugs to use as a model to examine potentially modifiable system characteristics that facilitate the occurrence of medication errors with drugs having a low therapeutic ratio. Identification of these characteristics should reduce not just the substantial adverse drug events associated with nephrotoxic antibiotics, but also those associated with other classes of medications used in the hospital setting. Aminoglycoside monitoring programs have been implemented widely as a system intervention in response to these concerns. Yet, aminoglycoside nephrotoxicity still continues. A hospital-based case-control study is proposed nested in a dynamic cohort of patients receiving aminoglycoside antibiotics. Subjects with acute renal failure and controls without acute renal failure will be enrolled in the study during 3+ years of recruitment, yielding a sample size sufficient to detect even small but clinically meaningful associations between predisposing factors and acute renal failure. Our specific aims are focused on the identification of the system-based predisposing factors for inappropriate aminoglycoside antibiotic monitoring and dosing that leads to acute renal failure. In particular, we will examine: 1) the failure to use pharmacokinetic monitoring; 2) delays in initiating pharmacokinetic monitoring; 3) failure to implement recommendations from the pharmacokinetic monitoring service; and 4) pharmacokinetic monitoring service characteristics/procedures systems. The specific hypotheses underlying these specific aims are: 1) attention to the recommendations arising from pharmacokinetics monitoring early in the course of aminoglycoside antibiotic therapy will reduce medication errors leading to acute renal failure, and 2) meticulous attention to measuring aminoglycoside antibiotic blood levels according to principles of pharmacokinetics will reduce medication errors leading to acute renal failure. A secondary set of aims will seek to identify other potentially modifiable predisposing factors for errors leading to acute renal failure among patients receiving aminoglycoside antibiotics, including interactions among health care personnel, type of clinical service, and other potentially modifiable predisposing factors for acute renal failure. This study will be integrated with each of the other projects of this program, by virtue of their complementary research themes all directed at the overarching goal of improving patient safety through the application of epidemiologic research methods to identify the factors predisposing to medication errors. In addition, this project will draw on the resources of all four cores for the implementation of this study and, ultimately, dissemination of its findings to all relevant stakeholders.